The purpose of the proposed research project is: (1) to obtain information about the structures and catalytic mechanisms of dihydrofolate reductase and methionine synthetase; (2) to obtain information about the transport of folate compounds (particularly folate 5-methyl tetrahydrofolate, and amethopterin) and vitamin B12 into cells; and (3) to utilize the above information in the design of new cancer chemotherapeutic regimens. BIBLIOGRAPHIC REFERENCES: Synthesis of a Fluorescent Derivative of Amethopterin. G.R. Gapski, J.M. Whiteley, J.I. Rader, P.L. Cramer, G.B. Henderson, V. Neef and F.M. Huennekens (1975) J. Med. Chem. 18, 526-528. Transport of Vitamin B12 into Mouse Leukemia Cells. P.M. DiGirolamo and F.M. Huennekens (1975) Arch. Biochem. Biophys. 168, 386-393.